A Review of Aeruginascin and Potential Entourage Effect in Hallucinogenic Mushrooms
Bibliographic record
Abstract
Introduction The 5-HT 2A agonist classic psychedelic, psilocybin (O-phosphoryl-4-hydroxy-N,N-dimethyltryptamine) is a tryptophan, indole-based alkaloid present in up to 2% of certain hallucinogenic “magic” mushroom species; typically Psilocybe azurescens, semilanceata, and cyanescens,. In addition, mushrooms may contain psilocin (4-hydroxy-N,N-dimethyltryptamine). Both are indolylalkylamines (tryptamines); other naturally occurring tryptamine compounds include norbaeocystin, baeocystin, norpsilocin, and aeruginascin. A putative synergistic contribution of these compounds has been referred to as the “entourage” effect. Aeruginascin (N,N,N-trimethyl-4-phosphoryloxytryptamine) is found naturally in Inocybe aeruginascens and Pholiotina cyanopus mushroom species and ingestion reportedly invokes elevation in mood without accompanying hallucinogenic effects: Objectives To review the pharmacology of aeruginascin and putative entourage effect. Methods The extant literature on aeruginascin was reviewed and discussed. Results Methylation of aeruginascin results in an active metabolite, 4-hydroxy-N,N,N-trimethyltryptamine (4-HO-TMT) which has been shown to bind at 5-HT 1A , 5-HT 2A , and 5-HT 2B receptors with Inhibition Constants (K i ) of 4400, 670, and 120 nM respectively; compared with psilocybin’s binding of 567.4, 107.2 and 4.6 nM respectively. Further, 4-HO-TMT does not bind at the 5-HT 3 receptor, and as a quaternary trimethylammonium compound it is less likely to be able to cross the blood-brain-barrier (BBB). Conclusions There are very limited data with respect to the pharmacology of aeruginascin. Its activity at serotonin receptors is less by several orders of magnitude than psilocybin and it has potentially less brain penetrance. Given that it is found in different mushrooms species the data would suggest that its direct contribution to any entourage effect is limited. Further research in needed into other naturally occurring tryptamine compounds. Disclosure PC is a member of the Scientific Advisory Board of Zylorion. AA, EB, JC, CE have no disclosures to report.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".